The former specific aims were: 1) To test the hypothesis that the increase in malonyl-CoA caused by an excess of glucose is related to cytosolic citrate. 2) To explore the possibility that other kinases interact with AMPK in regulating ACC activity and fatty acid oxidation in muscle. 3) To extend preliminary observations suggesting that malonyl-CoA decarboxylase is regulated by phosphorylation and that its activity is increased in muscle contraction. The subcellular distribution of MCD and whether its activity is regulated by AMPK or other kinases activated by muscle contraction will be assessed. 4) To determine if the high concentration of malonyl-CoA that has been found in muscle mitochondria is due to transport from the cytosol or de novo synthesis. 5) To evaluate whether alterations in one or more of the mechanisms we have defined can explain elevated levels of malonyl-CoA in muscle in situations for which no definitive explanation currently exists such as the Dahl-salt-sensitive rat. The investigators have responded to the reviewer's